Outlook For Graphene-Based Desalination Membranes

We discuss here next-generation membranes based on graphene for water desalination, based on the results of molecular simulations, application of nanofabrication technologies, and experiments. The potential of graphene to serve as a key material for advanced membranes comes from two major possible advantages of this atomically thin two-dimensional material: permeability and selectivity. Graphene-based membranes are also hypothetically attractive based on concentration polarization and fouling, and graphene's chemical and physical stability. Further research is needed to fully achieve these theoretical benefits, however. In addition, improvement in the design and manufacturing processes, so to produce performance and cost-effective graphene-based desalination devices, is still an open question. Finally, membranes are only one part of desalination systems, and current processes are not optimized to take full advantage of the higher selectivity and permeability of graphene. New desalination processes are, therefore, needed to unlock the full benefits of graphene

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Modulation of paclitaxel transport by flavonoide derivatives in human breast cancer cells. Is there a Correlation Between Binding Affinity to NBD of P-gp and Modulation of Transport?

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The effect of flavonoid derivatives on doxorubicin transport and metabolism

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